Multimodal evaluation of in vivo magnetic resonance imaging of myocardial restoration by mouse embryonic stem cells.
OBJECTIVE
Mouse embryonic stem cells have demonstrated potential to restore infarcted myocardium after acute myocardial infarction. Although the underlying mechanism remains controversial, magnetic resonance imaging has provided reliable in vivo assessment of functional recovery after cellular transplants. Multimodal comparison of the restorative effects of mouse embryonic stem cells and mouse embryonic fibroblasts was performed to validate magnetic resonance imaging data and provide mechanistic insight.


METHODS
SCID-beige mice (n = 55) underwent coronary artery ligation followed by injection of 2.5 x 10(5) mouse embryonic stem cells, 2.5 x 10(5) mouse embryonic fibroblasts, or normal saline solution. In vivo magnetic resonance imaging of myocardial restoration by mouse embryonic stem cells was evaluated by (1) in vivo pressure-volume loops, (2) in vivo bioluminescence imaging, and (3) ex vivo TaqMan (Roche Molecular Diagnostics, Pleasanton, Calif) polymerase chain reaction and immunohistologic examination.


RESULTS
In vivo magnetic resonance imaging demonstrated significant improvement in left ventricular ejection fraction at 1 week in the mouse embryonic stem cell group. This finding was validated with (1) pressure-volume loop analysis demonstrating significantly improved systolic and diastolic functions, (2) bioluminescence imaging and polymerase chain reaction showing superior posttransplant survival of mouse embryonic stem cells, (3) immunohistologic identification of cardiac phenotype within engrafted mouse embryonic stem cells, and (4) polymerase chain reaction measuring increased expressions of angiogenic and antiapoptotic genes and decreased expressions of antifibrotic genes.


CONCLUSIONS
This study validates in vivo magnetic resonance imaging as an effective means of evaluating the restorative potential of mouse embryonic stem cells.
Hendry
Stephen L
SL
Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford University, Stanford, California 94305, USA.
van der Bogt
Koen E A
KE
Sheikh
Ahmad Y
AY
Arai
Takayasu
T
Dylla
Scott J
SJ
Drukker
Micha
M
McConnell
Michael V
MV
Kutschka
Ingo
I
Hoyt
Grant
G
Cao
Feng
F
Weissman
Irving L
IL
Connolly
Andrew J
AJ
Pelletier
Marc P
MP
Wu
Joseph C
JC
Robbins
Robert C
RC
Yang
Phillip C
PC
D000818:Animals; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000473:pathology / Q000637:transplantation*; D005260:Female; D005347:Fibroblasts / Q000637:transplantation; D006084:Graft Rejection; D006085:Graft Survival; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D016513:Mice, SCID; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology* / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000473:pathology; D011897:Random Allocation; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D033581:Stem Cell Transplantation / Q000379:methods*; D013318:Stroke Volume; D020257:Ventricular Remodeling / Q000502:physiology*